Most human protein therapeutics require frequent dosing due to rapid clearance of the proteins from the body. Development of second generation protein pharmaceuticals that can be ingested less frequently is of considerable interest to patients and healthcare providers. We propose to create long-acting forms of interferons alpha, beta and gamma by creating large forms of the proteins with longer circulating half- lives. We believe these modified proteins will possess biological activities equal or superior to the corresponding natural proteins in vivo, but will require less frequent dosing, on the order of once every two to four weeks, rather than daily or every other day. During Phase I we will construct the modified interferon proteins and demonstrate that they possess wild type in vitro bioactivities. During Phase II, we will develop manufacturing processes to produce sufficient quantities of the modified proteins for testing in animal disease models. The improved characteristics of the novel proteins will reduce the amount of protein required per patient, improve patient compliance and quality of life and result in considerable cost savings to patients and healthcare providers. These proteins will find utility in treating cancer, neurological disorders and infectious diseases. PROPOSED COMMERCIAL APPLICATION: Recombinant human interferons are used to treat a wide variety of cancers, viral diseases such as Hepatitis B and C and neurological diseases such as Multiple Sclerosis. Worldwide sales of recombinant interferons were in excess of $2 billion in 1997. The modified interferon proteins under development will require much less frequent dosing that existing products, providing significant cost savings to patients and healthcare providers. Additional expected benefits include improved drug efficacy, reduced toxicity and improved patient quality of life.